Misc PG expansion / contraction & drug concentrations

speedballs_over

Bluelighter
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TL: Does anyone have a referenced value for the temperature related coefficient of expansion (how much volume increases for PG as temp rises)? Assume no solute effect, unless you find specific values for common PG solutions people here would prepare. That would be very cool.

Mods - please move if you feel this is too complex for OD, I think not, it's just a long post explaining one aspect of physical chemistry that has a possible effect in HR considerations. Thank you.

Some of us use very high quality glassware and such to prep volumetric solutions. And hopefully vendors do as well. So, depending upon the answer to this it could be nothing or an issue we don't take into account, but should. If the value is high enough then solutions prep'd at higher temps then later consumed at lower temps* would be getting somewhat more of the solute, be it fentanyl, c-lam, etiz, etc...

*as much as 50-75 °C lower in my case, from prep to measure for consumption.

I don't think the effect is much but we should know, it could matter and help resolve some vendor / researcher disagreements, if it's significant.

If there's a vendor out there that preps PG solutions on a hot stir plate (at 50°C or so) then cools and quantifies (HPLC) the resulting solution at RT, I'd expect an assay value above 100% of theoretical, unless result corrected for this effect.

The issue at hand is for volumetric dosing. For example water has an unusual value, it contacts very slightly until freezing, then expands at just about 0°C. Hence, ice floats. This is *very* unique to water.

Most (all?) other liquids observe a positive volume increase to increase in temp value. I *believe* I noticed this recently with PG when I prepared PG diclaz solution in a volumetric flask using 99% PG food grade & grade A lab glass. As my solution cooled the volume dropped well below the volumetric line. Indicating some contracting, and thus concentration of the solution. But how much, I didn't measure, I suppose I could (approx. answer right there).?

This seems normal to me with my experience using dozens of solvents in the lab to prepare pure drugs and inactive ingredients for analytical analyses (HPLC ,GC, ICP, UV/VIS...), as pharmaceutical formulation chemist for the genetic drug industry. We always tightly controlled lab temp and our equipment always noted the temp of solutions being analysed or we did it ourselves. We nearly always prep'd & analyzed at RT except for very fragile cmpds. Those we prep'd and analysed at same temp, well below RT, or corrected for this effect, after analyzing quickly.

To make this relative to real life think alcohol thermometers (red liquid) or mercury thermometers (no longer in use in most places), they are useful b/c they have "high" (relative to water) coefficients of expansion and thus reflect temp changes very nicely at our earth's temps - they neither freeze nor boil at earth's temps but they definitely expand and contract significantly and linearly (just look at a typical alcohol thermometer, the lines are equally apart at -40 to 100F).

This is the basis of my ?, how much does PG do this, if at all. Best number i can find is: 00032 (1/°F), but that's for ethylene glycol. Doesn't seem like much, but I haven't done the math b/w preparing a solution at say 50C (temp I prep PG solutions at) vs. its volume at 0 C or 0 F (freezer temp), I tend to dose at 38F - my refrigerator's temp. So how much more is my dose, e.g. how much more conc. is my solution after cooling to 0 C from 50 C, or occasionally only down to at room temp, 25 C? Are my doses nearly the same or significantly different? Could very much matter during a taper or for controlling dosing in any manner.

Volumetric dosing is still the wisest manner in my opinion, I just thought this a relevant ?. I apologize if it's been asked before, I'm pretty sure someone else looked into this, I can't find the value for PG and don't want to assume it's = to Et-glycol, b/c it likely isn't. I'll try to find my Merck Index while you all answer this for us. If I find it, I'll post calcs and you all can dble check them and decide amongst yourselves if it's significant.

? is, how significant is the change per degree? Is it linear or logarithmic (I suspect linear).

Is it enough to make dosing imprecise at different temps? I like to keep 1mg/mL diclaz (in PG) in the refrigerator if it's for daily use, as it may be sensitive to light and heat, maybe more so than other benzos. I knew from analytical work that chlordiazpoxide (Librium) degrades significantly in a day at stnd RT and pressure, in 50/50 water/ethanol. I believe the main degradant is diazepam, but could be wrong. That's twenty five years ago I was analyzing librium capsules.

This could be significant for dosing. I suspect not too much or we'd have noted as a community the differences. PG definitely gets more viscous as it loses heat but that doesn't equate to expansion AFAIK across all liquids and doesn't answer the ?. It just begs it.

Can someone with more current knowledge & the magic number chime in? Thank you.

I hope readers understand my ?, and it's implications. Keeping a solution at cooler temps and in the dark is advised for most solutions to maintain solute stability (solute = for example, etizolam). Then on warming it expands in volume, and vice-versa, often stability and solution stability is easy to check, analyze and store for a month and re-analyze (using highly selective methods HPLC, not a standalone UV/VIS). A vendor working with an ISO certified lab could do this work, we do really need to know... But i digress...

Many new pharms have been discovered by looking at degradants and metabolites for physiological activity.

My main points are keeping solutions cool and dark is almost always wiser than the alternatives, freezing isn't advised but both ethanol and PG have very low freezing points vs. typical refriger temps. But expansion / contraction of any solution changes the concentration, sorry if that's obvious to the reader.

Thanks!
 
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